^
    over2years
    "RB-reactivator screening" as a novel cell-based assay for discoveries of molecular targeting agents including the first-in-class MEK inhibitor trametinib (trade name: Mekinist). (PubMed, Pharmacol Ther)
    Using the screening systems for agents that up-regulate the expression of p15, p27, and p21, we discovered the novel MEK inhibitor trametinib, the novel RAF/MEK inhibitor CH5126766/RO5126766/VS-6766, and the histone deacetylase inhibitor YM753/OBP-801, respectively...The combination of trametinib and the BRAF inhibitor dabrafenib was approved for advanced BRAF mutant melanoma in the USA, EU, Japan, and many other countries...In 2018, this combination was also approved for locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer in the USA after it had been granted Breakthrough Therapy Designation by the FDA. I describe here the characterization of our original screening system, RB-reactivator screening, by which these three molecular-targeting agents that advanced into clinical trials were identified.
    Review • Journal
    |
    CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    BRAF mutation • BRAF V600 • CDKN1B expression
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • avutometinib (VS-6766) • spiruchostatin A (OBP-801)
    over2years
    The histone deacetylase inhibitor OBP-801 has in vitro/in vivo anti-neuroblastoma activity. (PubMed, Pediatr Int)
    Overall, OBP-801 induces M-phase arrest and apoptosis in neuroblastoma cells via mitotic catastrophe. Our results indicate that OBP-801 is a promising therapeutic agent with fewer adverse effects for patients with neuroblastoma.
    Preclinical • Journal • Epigenetic controller
    |
    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)
    |
    MYCN amplification
    |
    spiruchostatin A (OBP-801)
    4years
    The novel histone deacetylase inhibitor OBP-801 induces apoptosis in rhabdoid tumors by releasing the silencing of NOXA. (PubMed, Mol Cancer Ther)
    In conclusion, OBP-801 induces apoptosis in RT cells by epigenetically releasing the silencing of NOXA, which is a key mediator of RT apoptosis. The epigenetic approach for NOXA silencing with OBP-801 is promising for RT treatment.
    Journal
    |
    TP53 (Tumor protein P53) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CASP3 (Caspase 3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)
    |
    spiruchostatin A (OBP-801)